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Zebrafish: A possible tool to evaluate bioactive ions
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)
2015 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 19, 10-14 p.Article in journal (Refereed) Published
Abstract [en]

Zebrafish is a well-established model organism with a skeletal structure that highly resembles mammalian bone. Yet its use in the research field of biomaterials has been limited. One area that could benefit from this model system is the evaluation of ionic dissolution products from different materials. As a proof of concept we have evaluated the effect of silicate ions on the zebrafish larvae and compared it to a well-known osteblastic cell line, MC3T3-E1 subclone 14. We have shown that sodium metasilicate (125 mu M and 625 mu M) induces more mineralisation in a dose-dependent manner in zebrafish larvae, 9 days post fertilisation as compared to the non-treated group. Moreover the same trends were seen when adding sodium metasilicate to MC3T3-E1 cultures, with more mineralisation and higher ALP levels with higher doses of silicate (25, 125 and 625 mu M). These results indicate the feasibility of zebrafish larvae for ionic dissolution studies. The zebrafish model is superior to isolated cell cultures in the aspect that it includes the whole bone remodelling system, with osteoblasts, osteoclasts and osteocytes. Zebrafish could thus provide a powerful in vivo tool and be a bridge between cell culture systems and mammalian models.

Place, publisher, year, edition, pages
2015. Vol. 19, 10-14 p.
Keyword [en]
Zebrafish, Silicon, MC3T3-E1, Bone mineralisation
National Category
Medical Materials
URN: urn:nbn:se:uu:diva-245779DOI: 10.1016/j.actbio.2015.03.010ISI: 000354152100002PubMedID: 25770927OAI: oai:DiVA.org:uu-245779DiVA: diva2:792703
Swedish Research Council, GA 621-2011-3399
Available from: 2015-03-04 Created: 2015-02-28 Last updated: 2015-06-23Bibliographically approved
In thesis
1. Additives Increasing the Bone-Forming Potential around Calcium Phosphate Cements: Statin, Strontium and Silicon
Open this publication in new window or tab >>Additives Increasing the Bone-Forming Potential around Calcium Phosphate Cements: Statin, Strontium and Silicon
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

More than one million people worldwide receive some kind of bone graft each year. Grafts are often needed following bone tumour removal or traumatic fractures to fill voids in the bone and to aid in the healing process. The most common method involves bone transplantation, in which bone tissue is taken from one site to fill the defect in another site. The procedure thus involves two surgeries, which leads to an increased risk of complications. New, synthetic graft materials that can be used to fill defects and minimise the complications associated with bone tissue harvesting are therefore necessary. The synthetic materials available today lack the inherent biological factors of bone that stimulate the bone regeneration process. Much of today’s research concerning synthetic bone graft materials aims to solve this issue and researchers have suggested several different strategies.

The purpose of this thesis is to improve the performance of acidic calcium phosphate cements, which are materials used as synthetic bone grafts. By combining these cements with drugs or ion additives, local delivery could be achieved with the potential to stimulate bone formation. Two different combinations were attempted in this thesis: cement in combination with simvastatin, or cement in combination with strontium halide salts. Both simvastatin and strontium are known to positively affect bone formation. The efficacy of the cements with the additives was evaluated using different bone cell cultures. The results regarding simvastatin showed that the cement’s mechanical property was not affected upon drug loading, and that the drug was released by a diffusion-controlled mechanism. Moreover, results showed that simvastatin stimulated the bone-forming cells (osteoblasts) to produce more bone tissue, while it inhibited bone-degrading cells (osteoclasts) from degrading the cement. These findings suggest that simvastatin could aid in the bone regeneration process in the local area surrounding the cement.

The main purpose of the study using strontium halide salts was to increase the cement’s X-ray contrast, which is a property used to monitor cement during injection. In addition, strontium is believed to positively affect bone cells. The X-ray contrast did increase after the addition of 10 wt% strontium bromide or strontium iodide, while the cell study results did not indicate any significant effects on the bone-forming cells.

In the last section of this thesis, zebrafish were used as a model to evaluate bone formation upon treatment with degradation products from synthetic bone grafts. The zebrafish is a small organism with 70 % gene homology to humans; due to its transparency, fast development and ease of handling, it is an interesting model for high-throughput studies. Silicate, which is an ionic degradation product of many different bone substitute materials, was used as a proof-of-concept to visualise bone formation in these fish. The results showed an increased bone formation upon treatment with 0.625 μM silicate ions. The results suggest that this model could be used as a complement to bone cell culture studies in pre-clinical evaluations of the degradation products of bone substitute materials, thus helping researchers to design materials with degradation products that could stimulate bone formation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 69 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1232
Calcium Phosphate Cements, Osteoblast, Osteoclast, Monetite, Zebrafish, Simvastatin, Strontium, Silicon
National Category
Medical Materials
Research subject
Engineering Science with specialization in Materials Science
urn:nbn:se:uu:diva-246289 (URN)978-91-554-9183-3 (ISBN)
Public defence
2015-04-22, Häggsalen, Ångströmlaboratoriet, Uppsala, 13:00 (English)
Available from: 2015-03-31 Created: 2015-03-04 Last updated: 2015-04-17

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Montazerolghaem, MaryamEngqvist, HåkanKarlsson Ott, Marjam
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